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Multiplicity of Sites for Extrathymic T-cell Differentiation

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In addition to an intrathymic pathway of T-cell differentiation, extrathymic pathways of T-cell differentiation have been found to exist at multiple sites in the living bodies of both mice and humans. Such sites include the sinusoids in the liver, intraepithelial sites in the intestine, the splenic red pulp, the thymic medulla, the decidua in the uterus, and the omentum in the peritoneal cavity. Although extrathymic pathways are minimal in youth, they become predominant with aging and under conditions of bacterial infections, pregnancy, malignancies and autoimmune diseases. Since T cells with extrathymic properties are present even in the thymic medulla, and all of them carry many properties of primitive T cells irrespective the sites where they exist, their differentiation pathways should be termed "primitive pathways of T-cell differentiation" rather than extrathymic pathways. In this review, we introduce the phenotypic and functional properties of these primitive T cells and discuss why such primitive T cells exist at multiple sites.

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